The goal of this research program is to analyze cell growth and development. Each project in the program uses defined cell populations to permit an integrated genetic and biochemical approach. Within this common framework we are addressing several problems. The prokaryote Caulobacter expresses different sets of genes at different stages of its cycle. The mechanism of temporal control of gene expression in this organism is being studied by examining the organization of the genome as a function of the cell cycle. Both Caulobacter and budding yeast couple the cell division cycle to membrane biogenesis. The coupling mechanisms in both cells will be analyzed by studying mutants conditionally defective in the biosynthesis of mebrane lipids. Chromosomal mutations of E. coli that prevent the expression of conjugative plasmid functions will be used to study the relation between gene expression and envelope biogenesis. The genes altered by these mutations will be cloned, their gene product identified and the role of these gene products in the synthesis and processing of envelope proteins determined. The role of specific E. coli DNA binding proteins in DNA replication and repair will be studied by analyzing strains carrying mutations in one of these proteins as well as by purifying the protein and characterizing its functions in DNA replication and repair in vitro. The relation between positional information and patterns of differentiation in multicellular aggregates will be studied in Hydra and Dictyostelium. The stem cell system in Hydra will be studied in order to elucidate the effect of position on the probability of stem cell self-renewal. Dictyostelium will be used to identify specific morphogenetic factors and to determine their mechanism of action.